The University of Cape Town Clinical Trials Unit (UCTCTU) will successfully contribute to the scientific needs of the National Institutes of Health and associated Clinical Trial Networks for the following significant reasons: The CTU presents 6 well established diverse clinical research sites led by an experienced team and an ability to respond to the epidemics of HIV, TB and associated conditions in both prevention and treatment research involving a broad range of populations including key populations such as MSM and adolescents. The clinical research sites exist in communities where the burden of HIV, TB, STI and non-communicable disease are as high as or higher than anywhere in the world. Two of the clinical research sites are already DAIDS accredited and the other 4 are highly functional sites sponsored by a range of other well-recognized networks. The UCTCTU and its research sites occur in one South African province with a well-functioning, cooperative health department. The sites all have access to some of the best laboratories, and arguably the finest scientific expertise and best medical diagnostic and investigative resources in the country. The CTU is accommodated and supported by an institution ranked the best university in Africa and a Health Science faculty recently ranked in the top 50 worldwide. The efficiencies and synergies of this exciting and broad reaching consortium of clinical sites is invoked by the fact that all the sites are components of the University of Cape Town thus having a shared management platform and all sites and CTU core are within a short drive. In this re-application, the experienced team at the DTHC has extended collaborations to other well established clinical research groups in the Health Science Faculty at UCT and expanded the CTU to the proposed UCTCTU which will service 6 research sites and 5 networks with, in addition, an interest in antimicrobial resistance. RELEVANCE: The UCT Clinical Trials Unit is described here with 6 pluripotent Clinical Research Sites in and around Cape Town will be able to contribute to the international and NIH scientific agenda by conducting excellent clinical trials and research in treatment, prevention and management of HIV, TB and related infections and conditions. This globally relevant quest for novel and improved ways to treat and prevent HIV/TB will also significantly impact the lives of individuals in the heavily burdened communities in Cape Town.